Journal
TOXICOLOGY LETTERS
Volume 267, Issue -, Pages 21-31Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2016.12.015
Keywords
4-nonylphenol; Sertoli cells; Autophagy; AMPK; mTOR-p70S6K/EBP1
Categories
Funding
- National Natural Science Foundation of China [81372960, 81172623]
- China Postdoctoral Science Foundation [2016M602310]
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The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the nursemaid cells for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100 mg/kg body weight/2 days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10 mu M Compound C or AMPI kappa alpha l siRNA pre-treatment effectively attenuated autophagy and reversed AMPK-mTOR-p70S6K/4EBP1 signaling in NP-treated SCs. Co-treatment with 1 mM AICAR remarkably strengthened NP-induced autophagy and mTOR inhibition in SCs. Together, these data suggest that NP stimulates Sertoli cell autophagy and inhibits mTOR-p70S6KRIEBP1 activity through AMPK activation, which is the potential mechanism responsible for the regulation of testis function and differentiation following NP exposure. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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